Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro.
Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro.
复制标题
艰难梭菌毒素 B 在体外破坏人结肠上皮方面比毒素 A 更有效。
DOI：
10.1172/jci117885
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
LaMont,JT
中科院分区：
文献类型：
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作者：
Riegler,M;Sedivy,R;Pothoulakis,C;Hamilton,G;Zacherl,J;Bischof,G;Cosentini,E;Feil,W;Schiessel,R;LaMont,JT
毒素A而不是毒素B似乎介导艰难梭菌肠炎动物模型中的肠损伤。本研究的目的是研究纯化的C.艰难梭菌毒素A和B对人结肠粘膜的影响。将组织内腔暴露于16-65 nM毒素A和0.2-29 nM毒素B 5 h可引起剂量依赖性上皮损伤。与基线相比，32 nM毒素A的电位差、短路电流和电阻分别降低76、58和46%，3 nM毒素B的电位差、短路电流和电阻分别降低76、55和47%（P < 0.05）。3 nM毒素A未引起电生理学变化。与对照组相比，暴露于32 nM毒素A和3 nM毒素B后，[3 H]甘露醇的渗透性增加了16倍（P < 0.05）。光镜和扫描电子显微镜暴露后，无论是毒素显示斑片状损伤和脱落的浅表上皮细胞，而隐窝上皮保持完整。鬼笔环肽染色切片的荧光显微镜检查表明，这两种毒素引起的破坏和凝聚的细胞F-肌动蛋白。我们的研究结果表明，人类结肠对毒素B的损伤作用比毒素A敏感约10倍，这表明毒素B在C的发病机制中可能比毒素A更重要。人类的艰难性结肠炎图片
Toxin A but not toxin B, appears to mediate intestinal damage in animal models of Clostridium difficile enteritis. The purpose of this study was to investigate the electrophysiologic and morphologic effects of purified C. difficile toxins A and B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16-65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent epithelial damage. Potential difference, short-circuit current and resistance decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55, and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P < 0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is approximately 10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficile colitis in man.Images